The sequential arrangement of nucleosomes along the chromatin fiber is punctuated by highly nuclease-sensitive sites. We previously mapped such sites to the 5 feet terminus of several heat shock genes in Drosophila by a novel indirect end-labeling technique. Such preferentially accessible sites in chromatin may function as points of entry to the DNA for RNA polymerase and control proteins. In order to locate specific sequences to which these proteins might be bound, we have recently used indirect end-labeling in a new way to identify short, nuclease-resistant DNA sequences, and have found such "footprints" within hypersensitive sites in chromatin. To determine the functional relationship of 5 feet terminal hypersensitive sites in chromatin to gene activity, we have made a promising start in the development of an in vitro transcription system from Drosophila nuclei.